ADCETRIS 50 mg powder for concentrate for solution for infusion.
Each vial contains 50 mg of brentuximab vedotin.
After reconstitution (see section 6.6), each ml contains 5 mg of brentuximab vedotin.
ADCETRIS is an antibody-drug conjugate composed of a CD30-directed monoclonal antibody (recombinant chimeric immunoglobulin G1 [IgG1], produced by recombinant DNA technology in Chinese Hamster ovary cells) that is covalently linked to the antimicrotubule agent monomethyl auristatin E (MMAE).
Excipients with known effect
Each vial contains approximately 13.2 mg of sodium.
For the full list of excipients, see section 6.1.
Powder for concentrate for solution for infusion.
White to off-white cake or powder.
ADCETRIS is indicated for the treatment of adult patients with relapsed or refractory CD30+ Hodgkin lymphoma (HL):
1. following autologous stem cell transplant (ASCT) or
2. following at least two prior therapies when ASCT or multi-agent chemotherapy is not a treatment option.
ADCETRIS is indicated for the treatment of adult patients with relapsed or refractory systemic anaplastic large cell lymphoma (sALCL).
Brentuximab vedotin should be administered under the supervision of a physician experienced in the use of anti-cancer agents.
Posology
The recommended dose is 1.8 mg/kg administered as an intravenous infusion over 30 minutes every 3 weeks.
Renal impairment
The recommended starting dose in patients with severe renal impairment is 1.2 mg/kg administered as an intravenous infusion over 30 minutes every 3 weeks. Patients with renal impairment should be closely monitored for adverse events (see section 5.2).
Hepatic impairment
The recommended starting dose in patients with hepatic impairment is 1.2 mg/kg administered as an intravenous infusion over 30 minutes every 3 weeks. Patients with hepatic impairment should be closely monitored for adverse events (see section 5.2).
If the patient's weight is more than 100 kg, the dose calculation should use 100 kg (see section 6.6).
Complete blood counts should be monitored prior to administration of each dose of this treatment (see section 4.4).
Patients should be monitored during and after infusion (see section 4.4).
Treatment should be continued until disease progression or unacceptable toxicity (see section 4.4).
Patients who achieve stable disease or better should receive a minimum of 8 cycles and up to a maximum of 16 cycles (approximately 1 year) (see section 5.1).
Dose adjustments
Neutropenia
If neutropenia develops during treatment it should be managed by dose delays. See Table 1 below for appropriate dosing recommendations (see also section 4.4).
Table 1: Dosing recommendations for neutropenia
|
Severity grade of neutropenia
(signs and symptoms [abbreviated description of CTCAEa])
|
Modification of dosing schedule
|
|
Grade 1 (<LLN - 1500/mm3
<LLN - 1.5 x 109/L) or
Grade 2 (<1500 - 1000/mm3
<1.5 – 1.0 x 109/L)
|
Continue with the same dose and schedule
|
|
Grade 3 (<1,000 - 500/mm3
<1.0 - 0.5 x 109/L) or
Grade 4 (<500/mm3
<0.5 x 109/L)
|
Withhold dose until toxicity returns to ≤ Grade 2 or baseline then resume treatment at the same dose and schedule b. Consider growth factor support (G-CSF or GM-CSF) in subsequent cycles for patients who develop Grade 3 or Grade 4 neutropenia.
|
a. Grading based on National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v3.0; see Neutrophils/granulocytes; LLN= lower limit of normal
b. Patients who develop Grade 3 or Grade 4 lymphopenia may continue treatment without interruption.
Peripheral neuropathy
If peripheral sensory or motor neuropathy emerges or worsens during t
